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Purpose: To evaluate the initial and long-term impacts on cardio-metabolic health indicators of the Stand Up Victoria intervention — a 12-month, multicomponent workplace-delivered intervention that successfully reduced overall sitting time, primarily by increasing standing time. Methods: Office worksites (≥1km apart) from a single organization were cluster randomized to intervention (n=7) or control (n=7). Participants were 136 intervention and 95 control desk-based workers (5–39 per worksite; 68% women; mean±SD age = 45.6±9.4 years). Outcomes, assessed at baseline (0 months), three months, and 12 months, were 14 individual biomarkers of body composition, blood pressure, glucose metabolism, lipid metabolism and a composite overall cardio-metabolic risk score. Intervention effects were assessed by linear mixed models, accounting for repeated measures and clustering, baseline values and potential confounders. Missing data were multiply imputed. Significance was set at p<0.05, two-tailed. Results: No significant intervention effects were observed at three months. Significant effects, favoring intervention, were observed at 12 months for fasting glucose (-0.34, 95%CI -0.65, -0.03, p=0.028 mmol/L) and the overall cardio-metabolic risk score (-0.16, 95%CI -0.30, -0.03, p=0.019). Other intervention effects were typically weakly in favor of the intervention group, but were non-significant and estimated with wide confidence intervals. Conclusions: In “healthy” workers (not selected as having any specific health condition), a workplace intervention showed a small benefit for improving biomarkers of cardio-metabolic risk, but only with 12 months of intervention and not for all biomarkers. Long term facilitation of movement and standing at work may be a useful approach to reducing cardiovascular disease risk in the working population. The potential benefits for workers at high risk for cardiovascular disease (e.g., with diabetes) may be even greater and merit investigation.